Saliva-omics in plasma cell disorders- Proof of concept and potential as a non-invasive tool for monitoring disease burden.

Multiple Myeloma (MM), the second most highly diagnosed lymphoid cancer worldwide, is characterised by the uninhibited proliferation of terminally differentiated B-lymphocytes. Leading to the production of monoclonal proteins (M proteins) and the development of CRAB features (hypercalcemia, renal impairment, anaemia and bone lesions), MM is considered incurable as the vast majority of patients eventually show a relapse in symptoms. MGUS (Monoclonal Gammopathy of Unknown Significance) is considered the premalignant form of MM and, although 93% of MM patients exhibit M protein production associated with MGUS before diagnosis, little is known about the switch from premalignant to malignant disease. To explore this change in disease further, LC-MS/MS analysis was carried out to identify potential salivary biomarkers to monitor disease burden. FABP5 was detected in saliva as having a significant increase in abundance in both the MGUS to symptomatic MM switch and throughout disease progression in MM. This finding was validated using western blot analysis and ELISA analysis. SIGNIFICANCE: With infinite amounts of research carried out in the field of biomarker discovery in serum, saliva is a readily available resource which has been relatively unexplored. The identification of evident changes in saliva indicating disease progression solidifies the usefulness and potential saliva has as a mirror of disease state and progression. The identification of previously established MM serum biomarker in saliva further solidifies the relevance of saliva use for disease insight. The findings of this study also identified potential salivary biomarkers for change from premalignant MGUS to symptomatic MM, an area in MM that has been relatively untouched. The ability to monitor premalignant MGUS and to identify, preclinically, the stage at which disease is progressing will allow for stronger clinical decisions and precision medicine for patients. The subsequent potential use of saliva clinically ensures less invasive monitoring of disease.